Tampa, FL—Prophylactic salpingo-oophorectomy did not eliminate the risk for a rare but aggressive form of uterine cancer in women with BRCA1 mutations, according to a study reported at the 2014 Society of Gynecologic Oncology meeting.

Of 296 women who underwent the risk-reducing surgery, 4 subsequently developed high-risk uterine cancer. That number translates into an incidence rate 26 times higher than would have been expected in the general population.

The uterine cancer risk was limited to patients with BRCA1 mutations and did not involve women with BRCA2 mutations.

“While the absolute risk is still relatively low, it is much higher than we would have expected for these aggressive uterine cancers,” said Noah D. Kauff, MD, Director, Ovarian Cancer Screening and Prevention, Memorial Sloan Kettering Cancer Center, New York.

“Doctors should let their patients with BRCA1 mutations know that this report suggests they may be at risk for rare types of aggressive uterine cancer. However, whether or not a woman decides to have a hysterectomy at the time of risk-reducing salpingo-oophorectomy may depend on her age, prior cancer history and other risk factors.”

Prophylactic oophorectomy has become standard practice for women with BRCA mutations. The need for concomitant hysterectomy has remained controversial because of uncertainty about uterine cancer’s involvement in the BRCA-associated tumor spectrum, said Catherine A. Shu, MD, Gynecologic Oncology Fellow, Memorial Sloan Kettering Cancer Center, who reported the findings.

To examine uterine cancer risk in BRCA mutation carriers, Dr Shu and colleagues searched medical records of women who underwent BRCA testing from mid-1995 through the end of 2011 and subsequently underwent prophylactic oophorectomy. The researchers identified 525 patients with BRCA mutations, including 296 with BRCA1 and 229 with BRCA2.

After a median follow-up of almost 6 years, 4 patients were diagnosed with uterine cancer. Dr Shu said that 2.23 uterine cancers would have been expected.

All 4 uterine cancers occurred in patients with BRCA1 mutations, and all 4 cancers were high-risk—2 cases of serous cancer, and 1 each of carcinosarcoma and leiomyosarcoma. By contrast, less than 1 high-risk case (0.28) would have been predicted (P <.001).

An analysis of the results by tamoxifen use showed that 2 high-risk cases each occurred in tamoxifen users (0.092 expected; P = .004) and in women without a history of tamoxifen exposure (0.184; P = .015).

The National Comprehensive Cancer Network guidelines recommend prophylactic salpingo-oophorectomy for BRCA1 mutation carriers to reduce the risk for ovarian cancer and breast cancer. The recommendation does not include hysterectomy, which involves increased risks for bleeding, infection, and possibly long-term problems with bladder, bowel, or sexual function.

“It also was believed that uterine cancers that do develop following risk-reducing salpingo-oophorectomy were likely to be low risk. The new study suggests that may not be the case,” Dr Shu and colleagues concluded.